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Alison Murdoch

Publications and source records attributed to Alison Murdoch.

13 recordsLinked to original sources

A systematic review of the self-concept of children with cerebral palsy compared with children without disability.

Young people with cerebral palsy (CP) are often assumed to have low self-concept, in other words, they do not feel good about themselves. We systematically searched the literature to determine whether this assumption was supported by empirical research. Relevant trials were identified by searching electronic databases, and this was supplemented by citation tracking. Of 1355 papers initially identified, six met the criteria for review. Results showed that adolescent females with CP have a lower self-concept than females without disability in the domains of physical appearance (d = -1.16; 95% confidence interval [CI] -2.06 to -0.26); social acceptance (d = -1.24; 95% CI -2.15 to -0.33); athletic competence (d = -0.93; 95% CI -1.79 to -0.07); and scholastic competence (d = -0.86; 95% CI, -1.71 to -0.01). Adolescent females with CP may be an at-risk group owing to their vulnerable self-concept. Clinicians may need to monitor and implement appropriate intervention strategies with this group. There was insufficient evidence to conclude that children with CP, in general, have a lower global self-concept compared with those without disability.

Adolescent↗

Investigation of infertility management in primary care with open access hysterosalpingography (HSG): a pilot study.

Infertility affects one in seven couples in the United Kingdom. The National Institute for Clinical Excellence (NICE) issued guidance on the management of the infertile couple in February 2004, which included the statement "for the assessment of tubal damage, women not known to have co-morbidities (pelvic inflammatory disease, endometriosis or previous ectopic pregnancy) should be offered hysterosalpingography (HSG)". We made HSG available to six general practices in Newcastle upon Tyne as an open access investigation. Our aim was to evaluate the uptake of open access HSG, speed of access to specialist services and the quality of the information recorded in the referral letter. Using hospital clinical records we tracked the outcome of all infertile couples from the six pilot practices over a nine-month period. Of the 39 referrals identified, 10 women were eligible for open access HSG, of which six HSGs were organized by GPs. Couples who had open access HSG reached a diagnosis and management plan four weeks earlier than those who were referred directly (mean difference 4.0 weeks, 95% confidence interval (CI) -8.8 to 0.4 weeks). The information recorded in the referral letter was generally poor. However, all referrals made via the open access HSG service had the prerequisite tests done. Open access HSG allowed prompter access to specialist services with more complete information passed on in the referral letter. Open access HSG was used in 15% of all infertile couples and 60% of those who fitted the criteria for its use. Open access HSG together with semen analysis and endocrine blood tests may allow GPs to manage the initial stages of the infertile couple and make a diagnosis.

Adult↗

Downregulation of NANOG induces differentiation of human embryonic stem cells to extraembryonic lineages.

The homeobox transcription factor Nanog has been proposed to play a crucial role in the maintenance of the undifferentiated state of murine embryonic stem cells. A human counterpart, NANOG, has been identified, but its function and localization have not hitherto been described. We have used a combination of RNA interference and quantitative real-time polymerase chain reaction to study NANOG in human embryonic stem and embryonic carcinoma cells. Transfection of NANOG-specific small interfering RNAs reduced levels of NANOG transcript and protein and induced activation of the extraembryonic endoderm-associated genes GATA4, GATA6, LAMININ B1, and AFP as well as upregulation of trophectoderm-associated genes CDX2, GATA2, hCG-alpha, and hCG-beta. Immunostaining of preimplantation human embryos showed that NANOG was expressed in the inner cell mass of expanded blastocysts but not in earlier-stage embryos, consistent with a role in the maintenance of pluripotency. Taken together, our findings suggest that NANOG acts as a gatekeeper of pluripotency in human embryonic stem and carcinoma cells by preventing their differentiation to extraembryonic endoderm and trophectoderm lineages.

Blastocyst↗

Derivation of a human blastocyst after heterologous nuclear transfer to donated oocytes.

This paper describes the derivation of a blastocyst following heterologous nuclear transfer (NT) into a human oocyte. It also demonstrates that a major obstacle to continuing research in human NT is the availability of suitable human oocytes. In this study, 36 oocytes were donated by 11 women undergoing four different treatments and their developmental potential was evaluated after NT. The time from oocyte collection to NT seems to be crucial, and only oocytes that were enucleated within 1 h proved successful. After enucleation of oocytes, fusion with undifferentiated human embryonic stem cells and in-vitro culture, early cleavage and blastocyst development of fused complexes was observed. The DNA fingerprinting comparison of the donor cells and derived blastocyst revealed successful heterologous NT, since both oocytes and donor cells were recovered from different patients. It has therefore been demonstrated that NT can be achieved in humans, using heterologous donor nuclei and surplus and donated oocytes. However, if the promise of this new science is to achieve its potential in the foreseeable future, it will be necessary to identify new sources of oocytes that can be used immediately after retrieval.

Animals↗

The way forward.

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Female↗

An autogeneic feeder cell system that efficiently supports growth of undifferentiated human embryonic stem cells.

Human embryonic stem cells (hESCs) have great potential as a source of cells for therapeutic uses, but their culture requires the support of mouse or human cells, either directly as a feeder cell layer or indirectly as a source of conditioned medium in feeder-free culture systems. Unfortunately, the risks of cross-transfer of pathogens from xenogeneic or allogeneic feeders or cell by-products limit their medical applications. In addition, not all human feeders support the growth of hESCs equally well, and ethical concerns have been raised regarding the derivation of feeder cells from aborted human fetuses. We report here the culture of hESCs on a novel feeder cell system, comprising fibroblast-like cells derived from the spontaneous differentiation of hESCs. Isogenicity of the hESCs and hESC-derived fibroblasts was confirmed by micro satellite analysis. The nature of the hESC-derived fibroblasts was identified by the expression of specific markers. This feeder system permits continuous growth of undifferentiated and pluripotent hESCs, as demonstrated by the expression of specific hESC markers, by the formation of teratomas after injection of hESCs into severely combined immunodeficient mice, and by in vitro differentiation of hESCs into differentiated cells of ectodermal, endodermal, and mesodermal origin. Feeder cells derived from hESCs offers a potentially more secure autogeneic and genotypically homogenous system for the growth of undifferentiated hESCs.

Animals↗

Derivation, growth and applications of human embryonic stem cells.

Human embryonic stem (hES) cells are pluripotent cells derived from the inner cell mass cells of blastocysts with the potential to maintain an undifferentiated state indefinitely. Fully characterised hES cell lines express typical stem cell markers, possess high levels of telomerase activity, show normal karyotype and have the potential to differentiate into numerous cell types under in vitro and in vivo conditions. Therefore, hES cells are potentially valuable for the development of cell transplantation therapies for the treatment of various human diseases. However, there are a number of factors which may limit the medical application of hES cells: (a) continuous culture of hES cells in an undifferentiated state requires the presence of feeder layers and animal-based ingredients which incurs a risk of cross-transfer of pathogens; (b) hES cells demonstrate high genomic instability and non-predictable differentiation after long-term growth; and (c) differentiated hES cells express molecules which could cause immune rejection. In this review we summarise recent progress in the derivation and growth of undifferentiated hES cells and their differentiated progeny, and the problems associated with these techniques. We also examine the potential use of the therapeutic cloning technique to derive isogenic hES cells.

Blastocyst↗

Derivation of human embryonic stem cells from day-8 blastocysts recovered after three-step in vitro culture.

Human embryonic stem cells (hESCs) have been derived from the inner cell mass (ICM) of day 5-7 blastocysts and hold great promise for research into human developmental biology and the development of cell therapies for the treatment of human diseases. We report here that our novel three-step culture conditions successfully support the development of day-8 human blastocysts, which possess significantly (p <.01) more ICM cells than day-6 blastocysts. Plating of ICMs isolated from day-8 blastocysts resulted in the formation of a colony with hESC morphology from which a new hESC line (hES-NCL1) was derived. Our stem cell line is characterized by the expression of specific cell surface and gene markers: GTCM-2, TG343, TRA1-60, SSEA-4, alkaline phosphatase, OCT-4, NANOG, and REX-1. Cytogenetic analysis of the hESCs revealed that hES-NCL1 line has a normal female (46, XX) karyotype. The pluripotency of the cell line was confirmed by the formation of teratomas after injection into severely combined immunodeficient mice and spontaneous differentiation under in vitro conditions.

Adult↗

Homologue disjunction in mouse oocytes requires proteolysis of securin and cyclin B1.

Disjunction of pairs of homologous chromosomes during the first meiotic division (MI) requires anaphase-promoting complex (APC)-mediated activation of separase in budding yeast and Caenorhabditis elegans, but not Xenopus laevis. It is not clear which model best fits the mammalian system. Here we show that homologue disjunction in mouse oocytes is dependent on proteolysis of the separase inhibitor securin and the Cdk1 regulatory sub-unit cyclin B1. Proteolysis of both proteins was entirely dependent on their conserved destruction box (D-box) motifs, through which they are targeted to the APC. These data indicate that the mechanisms regulating homologue disjunction in mammalian oocytes are similar to those of budding yeast and C.elegans.

Animals↗

Human embryonic stem cells: an introduction.

Stem cell biology is currently one of the most promising areas of scientific development, possibly leading to new therapies for many diverse medical problems. A stem cell is a cell that has the potential to differentiate into other cell types and stem cell biology investigates the processes by which this differentiation is controlled. Some cells from adults have this potential, but it is only cells from very early embryos that have been shown to differentiate into all cell types. For this reason, interest has been focused on embryonic stem cells. This paper describes the process by which embryonic stem cells are derived and the associated practical problems. The potential benefits of embryonic stem cell biology are discussed. The need to develop cell nuclear replacement is considered since this may be necessary if stem cells are to be used to maximum benefit.

Cell Differentiation↗